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Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03333486
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : December 11, 2017
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Brief Summary:
This phase II trial studies how well fludarabine phosphate, cyclophosphamide, total body irradiation, and donor stem cell transplant work in treating patients with blood cancer. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient?s immune cells and help destroy any remaining cancer cells.

Condition or disease Intervention/treatment Phase
Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Acute Leukemia in Remission Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Acute Myeloid Leukemia With FLT3/ITD Mutation Acute Myeloid Leukemia With Gene Mutations Aplastic Anemia B-Cell Non-Hodgkin Lymphoma CD40 Ligand Deficiency Chronic Granulomatous Disease Chronic Leukemia in Remission Chronic Lymphocytic Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Myelomonocytic Leukemia Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Congenital Amegakaryocytic Thrombocytopenia Congenital Neutropenia Congenital Pure Red Cell Aplasia Glanzmann Thrombasthenia Immunodeficiency Syndrome Myelodysplastic Syndrome Myelofibrosis Myeloproliferative Neoplasm Paroxysmal Nocturnal Hemoglobinuria Plasma Cell Myeloma Polycythemia Vera Recurrent Non-Hodgkin Lymphoma Refractory Non-Hodgkin Lymphoma Secondary Acute Myeloid Leukemia Secondary Myelodysplastic Syndrome Severe Aplastic Anemia Shwachman-Diamond Syndrome Sickle Cell Disease T-Cell Non-Hodgkin Lymphoma Thalassemia Waldenstrom Macroglobulinemia Wiskott-Aldrich Syndrome Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Procedure: Peripheral Blood Stem Cell Transplantation Radiation: Total-Body Irradiation Phase 2

Detailed Description:


I. To evaluate the rate of relapse at 1 year in patients who receive haploidentical peripheral blood stem cells (PBSCs) after reduced intensity conditioning and post-transplant cyclophosphamide.


I. To evaluate safety including development of acute graft versus host disease (GVHD) and death at 100 days post-transplant, as well as other treatment related toxicities including chronic GVHD, engraftment rate, non-relapse mortality, progression free survival (PFS) at one year, and overall survival (OS) at one year, as compared with historical controls.


I. Correlative studies will include chimerism analysis by molecular analysis and evaluation of immune reconstitution by cytomegalovirus (CMV) dextramer analysis using flow cytometry.


Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -6 to -2 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients undergo total body irradiation (TBI) on days -1 and peripheral blood stem cell transplantation (PBSCT) on day 0.

After completion of study treatment, patients are followed up at 30 and 100 days.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 58 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of Haploidentical Allogeneic Stem Cell Transplantation Utilizing Mobilized Peripheral Blood Stem Cells
Actual Study Start Date : December 7, 2017
Estimated Primary Completion Date : September 6, 2021
Estimated Study Completion Date : September 6, 2022

Arm Intervention/treatment
Experimental: Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)
Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients undergo TBI on days -1 and PBSCT on day 0.
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586
Other: Laboratory Biomarker Analysis
Correlative studies
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo PBSCT
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • peripheral stem cell support
  • Peripheral Stem Cell Transplant
  • peripheral stem cell transplantation
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • Whole-Body Irradiation

Primary Outcome Measures :
  1. Relapse rate [ Time Frame: At 1 year ]

Secondary Outcome Measures :
  1. Engraftment rate [ Time Frame: At 1 year post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

  2. Incidence of acute graft versus host disease (GVHD) [ Time Frame: At 100 days post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

  3. Incidence of chronic GVHD [ Time Frame: At 1 year post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

  4. Overall survival [ Time Frame: At 1 year post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson. Will be obtained using the product-limit based Kaplan-Meier method.

  5. Progression free survival [ Time Frame: At 1 year from time of transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson. Will be obtained using the product-limit based Kaplan-Meier method.

  6. Transplant related mortality [ Time Frame: At 1 year post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

Other Outcome Measures:
  1. Immune reconstitution [ Time Frame: Up to 1 year ]
    Will be assessed by bone marrow transplantation SOC immunophenotyping panel and by analysis of cytomegalovirus-specific immunity.

  2. Myeloid and lymphoid chimerism expressed as a percentage of donor cells [ Time Frame: At 30 days ]
  3. Myeloid and lymphoid chimerism expressed as a percentage of donor cells [ Time Frame: At 100 days ]

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 75 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • The patient must have a diagnosis of one of the following (one must be yes):

    • Bone marrow failure disorders:

      • Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH):

        • SAA must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully-matched donor is not available
        • PNH should not be eligible for a myeloablative hematopoietic stem cell transplantation (HSCT)
      • Hereditary bone marrow failure disorders include Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, and congenital amegakaryocytic thrombocytopenia
    • Other non-malignant hematologic or immunologic disorders that require transplantation:

      • Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann?s thrombasthenia)
      • Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia)
      • Congenital primary immunodeficiencies (including but not limited to severe combined immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD40 ligand deficiency, T-cell deficiencies)
      • Hemoglobinopathies (including sickle cell disease and thalassemia
    • Acute leukemias:

      • Acute myeloid leukemia (AML) - antecedent myelodysplastic syndrome, secondary AML, high risk cytogenetic abnormalities or normal cytogenetics with high-risk molecular mutations (including but not limiting to Flt3-ITD mutation)
      • Acute lymphoblastic leukemia (ALL)
    • Chronic myelocytic leukemia:

      • Chronic phase (intolerant or unresponsive to imatinib and/or tyrosine kinase inhibitors)
      • Second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation
    • Myeloproliferative and myelodysplasia syndromes:

      • Myelofibrosis (with/without splenectomy) with intermediate to high risk features
      • Advanced polycythemia vera not responding to therapy
      • Myelodysplastic syndrome (MDS) with an International Prognostic Scoring System (IPSS) score of INT-2 or higher
      • MDS with lower IPSS scores Int-1 or less with severe clinical features; neutropenia, thrombocytopenia, high risk chromosome abnormalities (monosomy 7)
      • Secondary MDS with any IPSS score
      • Chronic myelomonocytic leukemia
    • Lymphoproliferative disease:

      • Chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) (recurrent or persistent) cytotoxic therapy refractory or with less than 6 months duration of complete response (CR) between courses of conventional therapy
      • Multiple myeloma (MM) progressive disease after auto bone marrow transplantation (BMT), tandem allo after prior auto
      • Waldenstrom?s macroglobulinemia (failed one standard regimen)
      • T or B cell lymphoma with poor risk features
      • Hodgkin disease:

        • Received and failed frontline therapy
        • Failed or not eligible for autologous transplantation
  • For all acute and chronic leukemias, lymphoproliferative diseases and Hodgkin?s disease: patient must be in documented complete remission, with restaging to include imaging and/or bone marrow aspirate/biopsy as clinically appropriate, within 30 days prior to the start of conditioning
  • Suitable related haploidentical donor identified:

    • Must be matched at least at 6 of 12 or 3 of 6 HLA antigens (A, B, DRB1)
    • Must not be matched at more than 8 of 12 HLA antigens
    • Recipient should not have HLA antibodies to potential donor; if the recipient does have HLA antibodies to the potential donor, an alternative donor is preferred; however, if there are no suitable alternative donors, the donor to whom the patient has HLA antibodies can be utilized as long as the antibody titer is less than 2000 median fluorescence intensity (MFI); if the titer is > or = to 2000 MFI, the recipient must undergo successful antibody desensitization prior to enrollment on this study; any patients who have demonstrated donor specific antibodies will not be evaluated for the end points measured in this study but will be followed for treatment related toxicities
  • Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% predicted, corrected for hemoglobin and/or alveolar ventilation
  • Left ventricular ejection fraction > 40%
  • Bilirubin, liver alkaline phosphatase, serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
  • Calculated creatinine clearance > 40 cc/min by the modified Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics
  • Have a Karnofsky (adult) or Lansky (for =< 16 years) performance status > 50%
  • Patient must be able to pass radiation evaluation (i.e.: able to receive 200 cGy)
  • Patients who have failed a prior autologous transplant are eligible; however, at least 90 days must have elapsed between the start of this reduced intensity conditioning regimen and the last transplant if patient had a prior autologous BMT
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Participant or legal representative must understand the investigational nature of this study and sign an independent ethics committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
  • In the case of a potential pediatric donor (< 18 years of age), as recommended by the Worldwide Network for Blood and Marrow Transplantation, donor evaluation and medical clearance for PBSC mobilization and collection must be performed by a pediatric hematologist (or pediatric oncologist) who is not the primary hematologist/oncologist for the patient (the potential recipient); if the physician who is evaluating the potential pediatric donor does not feel that it is safe for the potential donor to undergo PBSC mobilization and collection, or that it is otherwise not in the best interest of the potential donor to do so (an ethics consultation may be utilized as per the evaluating physician?s discretion), then the potential donor will not undergo PBSC mobilization and collection; if another suitable haploidentical donor cannot be found for the patient, then the patient will be ineligible for this study; PBSC collection on pediatric donors will be performed as per BMT standard of procedure (SOP) 312 - TA2007; donors must be at least 2.5 years of age at the time of PBSC mobilization for this study

Exclusion Criteria:

  • Participants who have had chemotherapy, radiation treatment and/or surgery 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier
  • Uncontrolled central nervous system (CNS) disease (for hematologic malignancies)
  • Child-Pugh class B and C liver failure
  • Concomitant active malignancy that would be expected to require chemotherapy within 3 years of transplant (other than non-melanoma skin cancer)
  • Patients who have received maximally allowed doses (given in 2 Gy fractionations, or equivalent) of previous radiation therapy to various organs; patients who previously have received a higher than allowed dose of radiation to a small lung, liver and brain volume, will be evaluated by the radiation oncologist to determine if the patient is eligible for study
  • Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient
  • Known human immunodeficiency virus (HIV) positive
  • Pregnant or nursing female participants
  • Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening
  • Patients with donor specific HLA antibodies with a titer greater than 2000 MFI (whether or not they have undergone a desensitization protocol)
  • Patients who have undergone a prior allogeneic hematopoietic or (other organ) transplant
  • Treating physician or considers the potential HLA haploidentical donor to be ineligible to receive G-CSF, and/or concern on the part of the treating physician for risk of harm to the potential donor with administration of G-CSF, and/or refusal by the potential donor (or donor?s guardian) to receive G-CSF
  • Any condition which in the investigator?s opinion deems the participant an unsuitable candidate to receive study drug
  • Received an investigational agent within 30 days prior to enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03333486

Contact: ASK RPCI 877-275-7724

United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Sophia R. Balderman    716-845-6972   
Principal Investigator: Sophia R. Balderman         
Sponsors and Collaborators
Roswell Park Cancer Institute
National Cancer Institute (NCI)
Principal Investigator: Sophia Balderman Roswell Park Cancer Institute

Responsible Party: Roswell Park Cancer Institute Identifier: NCT03333486     History of Changes
Other Study ID Numbers: I 40916
NCI-2017-01949 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 40916 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
First Posted: November 7, 2017    Key Record Dates
Last Update Posted: December 11, 2017
Last Verified: December 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Aplastic
Anemia, Diamond-Blackfan
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia, Hypoplastic, Congenital
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Neoplasm Metastasis
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Immunologic Deficiency Syndromes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Primary Myelofibrosis
Lymphoma, T-Cell
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile